crossing96/oncoscreening huggingface dataset:
The significance of microscopic bladder neck invasion in radical prostatectomies: pT4 disease?	INTRODUCTION: It is controversial whether microscopic invasion of the bladder neck (BN) has a high risk for biochemical progression following radical prostatectomy (RP). The tumor, node, and metastasis (TNM) classification for prostate cancer considers BN involvement to be pT4 disease, equivalent to rectal or external sphincter invasion, however, it does not specify whether the invasion is macroscopic or microscopic. MATERIALS AND METHODS: Clinicopathological findings were studied from 290 patients submitted to RP. The time to biochemical (prostate-specific antigen, PSA) progression-free outcome for patients with BN invasion was compared to patients with extraprostatic extension (EPE) or seminal vesicle invasion (SVI). A univariate Cox proportional hazards model was created and a final multivariate Cox proportional hazards model was developed to assess the influence of several variables simultaneously. RESULTS: BN invasion was present in 55/290 (18.96%) surgical specimens and 18/290 (6.2%) also showed positive surgical margins. Patients with microscopic BN invasion had significantly higher preoperative PSA, higher Gleason score, higher apical and circumferential positive surgical margins, more advanced pathological stage, and more extensive tumors. At 5 years 42%, 40%, and 27% of the patients with BN invasion, extraprostatic extension (EPE), and seminal vesicle invasion (SVI), respectively, were free of biochemical recurrence following RP. In multivariate analysis, BN invasion did not contribute for a higher relative hazard of PSA recurrence when added to EPE or SVI. CONCLUSION: BN invasion is associated with adverse clinicopathological findings. However, the biochemical-free outcome following RP is similar to patients with EPE but significantly better than patients with SVI. The findings of this study do not favor considering microscopic bladder neck invasion as stage pT4 but, probably, stage pT3a.	bladder
Structure-activity relationships and organ specificity in the induction of GST and NQO1 by alkyl-aryl isothiocyanates.	PURPOSE: To compare the ability of alkyl-aryl isothiocyanates (ITCs) to increase the activities of the Phase 2 detoxification enzymes NAD[P]H:quinone acceptor oxidoreductase 1 (NQO1) and glutathione S-transferases (GST) in rat tissues in vivo and in cells in vitro. MATERIALS AND METHODS: Twelve alkyl-aryl ITCs and the fully-reduced derivative of benzyl ITC (cyclohexylmethyl ITC) were administered to rats each day for 5 days. The animals were then killed and organs harvested. The ITCs were also evaluated in a bladder cell line in culture. The activities of NQO1 and GST in the organs and cells were measured. RESULTS: In vivo, the organ most susceptible to the inductive activity of the ITCs was the urinary bladder, with alpha-methylbenzyl ITC and cyclohexylmethyl ITC being the most effective. Inductive activity in the bladder in vivo did not, however, correlate with that in bladder cells in vitro. CONCLUSIONS: Induction of Phase 2 enzymes increases resistance to chemical carcinogenesis. ITCs could therefore be valuable chemopreventative agents, and the specificity of these substances toward the urinary bladder suggest that they could be particularly useful for protecting against bladder cancer. In this regard, alpha-methylbenzyl ITC and cyclohexylmethyl ITC could be especially valuable.	bladder
Familial and genetic risk of transitional cell carcinoma of the urinary tract.	Environmental exposures, including tobacco smoke and occupational exposure to aromatic amines, have been implicated in bladder cancer etiology. However, the pathogenesis of urinary bladder transitional cell carcinoma remains incompletely defined. In epidemiologic studies, family history confers a 2-fold increase in bladder cancer risk, but it is uncertain whether this represents evidence of a genetic and/or a shared environmental basis for familial aggregation. Polymorphisms in genes involved in the metabolism of environmental toxins (e.g., NAT2) clearly modify individual susceptibility to bladder cancer. A genetic predisposition has also been suggested by case reports describing multiple-case families, and the development of bladder cancer in association with several well-described Mendelian disorders (e.g., HNPCC, retinoblastoma). Here we update a previously reported family, report a new multiple-case kindred, critically review previously reported bladder cancer families, and the epidemiologic literature related to family history of transitional cell carcinoma of the urinary tract (TCCUT) as a risk factor, as well as provide a brief summary of genetic factors that have been implicated in TCCUT risk. We conclude that familial TCCUT is either very uncommon or significantly under-reported, perhaps on the assumption that this is an environmental rather than a genetic disorder. The interaction between multiple genetic and environmental factors has made it challenging to identify genetic components responsible for many common diseases; therefore, a proposed genome-wide association study (GWAS) for urinary bladder cancer may help to clarify the etiologic role of the candidate genetic pathways reviewed here, as well as characterize gene/environment interactions that contribute to TCCUT carcinogenesis.	bladder
Occupational exposure to solvents and gasoline and risk of cancers in the urinary tract among Finnish workers.	BACKGROUND: Bladder cancer (BC) is generally considered as an occupational disease, and some chemical exposures may also be associated with renal cell cancer (RCC). The aim of this study was to estimate the risk of cancers of the urinary tract in relation to occupational exposure to solvents and gasoline. METHODS: A cross-sectional cohort of all economically active Finns from the 1970 population census was followed up for BC (10,277 cases) and RCC (9,954 cases). Census occupations were assigned estimates of exposure to hydrocarbon (HC) solvents and gasoline with a job exposure matrix. Relative risk (RR) estimates were defined using Poisson regression models, adjusted for smoking and obesity. RESULTS: Exposure to solvents was positively associated with the incidence of BC in women but not in men. The RR estimates were above 1.2 in nearly all exposure categories of all exposures studied but a statistically significant excess was only seen for middle levels of chlorinated HC solvents (1.7; 95% CI = 1.2-2.5) and a low level of aromatic HC solvents (1.6; 95% CI = 1.3-2.1). The RR estimates for RCC were close to unity in all categories of exposure. CONCLUSIONS: Our findings suggest that occupational exposure to certain solvents may have an impact on BC risk. The risk of RCC does not appear to be altered by exposure to HC solvents or gasoline.	bladder
Livin may serve as a marker for prognosis of bladder cancer relapse and a target of bladder cancer treatment.	OBJECTIVES: To evaluate the expression of Livin in bladder cancer, investigate its clinical and prognostic implications, and explore the effect of gene Livin transfection on the proliferation and apoptosis in bladder cancer cells. METHODS: The expression of Livinalpha and beta was detected in 48 bladder cancer samples (G(1) in 23 cases, G(2) in 17 cases, and G(3) in 8 cases. Of the 48 cases, 17 developed relapse) and 15 non-tumor bladder tissues by Western blot and reverse transcription PCR (RT-PCR). Livinalpha-pcDNA3.1(+) was constructed and transfected into T24, BIU-87 and EJ bladder cancer cells. The clone activity of the transfected cells was detected by colony formation analysis. MTT was used to determine the cell proliferation assay. Flow cytometry and acridine orange staining were used to examine apoptosis. Caspase 3 activity assay was also measured. RESULTS: Expression of Livinalpha, but not beta, was detected in 19 of the 48 bladder cancer samples; G(1) was 39.13%, G(2) and G(3) were 41.18% and 37.50%, respectively, which showed no significant (P > 0.05), but not in 15 non-tumor bladder tissues. The positive rate of Livinalpha was significant higher in relapse tumors (58.82%) than in primary tumors (29.03%) (P < 0.05). By the end of 2 years follow-up, the relapse rate in Livin positive patients was 68.42%, and 37.93% in Livin negative group. The difference between the two groups was significant (P < 0.05). Additionally, overexpression of Livinalpha clearly stimulated cell proliferation and inhibited chemical induced apoptosis in bladder cancer cells. CONCLUSIONS: Livin may serve as a promising marker to identify the relapse risk in bladder cancer, and targeting Livin could offer a therapeutic benefit in apoptosis-inducing treatment.	bladder
Molecular profiling of angiogenesis in hypericin mediated photodynamic therapy.	BACKGROUND: Photodynamic therapy (PDT) involves the administration of a tumor-localizing photosensitizing drug, which is activated by light of specific wavelength in the presence of molecular oxygen thus generating reactive oxygen species that is toxic to the tumor cells. PDT selectively destroys photosensitized tissue leading to various cellular and molecular responses. The present study was designed to examine the angiogenic responses at short (0.5 h) and long (6 h) drug light interval (DLI) hypericin-PDT (HY-PDT) treatment at 24 h and 30 days post treatment in a human bladder carcinoma xenograft model. As short DLI targets tumor vasculature and longer DLI induces greater cellular damage, we hypothesized a differential effect of these treatments on the expression of angiogenic factors. RESULTS: Immunohistochemistry (IHC) results showed minimal CD31 stained endothelium at 24 h post short DLI PDT indicating extensive vascular damage. Angiogenic proteins such as vascular endothelial growth factor (VEGF), tumor necrosis growth factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha) and basic fibroblast growth factor (bFGF) were expressed to a greater extent in cellular targeting long DLI PDT compared to vascular mediated short DLI PDT. Gene expression profiling for angiogenesis pathway demonstrated downregulation of adhesion molecules - cadherin 5, collagen alpha 1 and 3 at 24 h post treatment. Hepatocyte growth factor (HGF) and Ephrin-A3 (EFNA3) were upregulated in all treatment groups suggesting a possible activation of c-Met and Ephrin-Eph signaling pathways. CONCLUSION: In conclusion, long DLI HY-PDT induces upregulation of angiogenic proteins. Differential expression of genes involved in the angiogenesis pathway was observed in the various groups treated with HY-PDT.	bladder
Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer.	Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual's susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case-control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19-48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19-1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12-1.81) and 1.71 (1.25-2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12-3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype.	bladder
Maintenance bacillus Calmette-Guérin in high-risk nonmuscle-invasive bladder cancer: how much is enough?	BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) immunotherapy is effective in preventing recurrence and progression in nonmuscle-invasive bladder cancer but the dosing schedule and duration of treatment remain empirical. The outcome of BCG therapy was prospectively evaluated on patients according to the number of maintenance cycles received. METHODS: Between 1997 and 2002, 111 patients with nonmuscle-invasive bladder cancer at high risk of recurrence and progression underwent transurethral resection followed by intravesical instillations of BCG. After an induction treatment of 6 weekly instillations, patients were scheduled to receive a 3-weekly maintenance treatment at the 3rd, 6th, 12th, 18th, 24th, 30th, and 36th month. At each visit a clinical assessment was obtained. RESULTS: Over a median clinical follow-up of 31 months, 43% of patients experienced recurrence and 8.1% progressed to muscle-invasive disease or metastasis. Only 1 patient received all scheduled instillations. Patients who received at least 3 maintenance BCG cycles had a significantly reduced risk of recurrence (hazard ratio [HR] = 0.23, P = .0064, adjusted for gender, age, and stage) compared with patients receiving only induction BCG. Twelve months after the end of maintenance, the estimated Kaplan-Meier recurrence-free survival was 89% for patients who received at least 3 maintenance BCG cycles, 67% for those who received 2 maintenance BCG cycles, and 41% for those who received only the induction BCG or 1 maintenance cycle (P = .0003). CONCLUSIONS: The results of this study suggest that a minimum of 3 cycles of maintenance BCG is required to significantly reduce the recurrence rate. It also suggests that more cycles may result in further improvements but the benefits may be outweighed by increasing side effects in some patients.	bladder
Oral acanthosis nigricans: case report and comparison with literature reports.	Acanthosis nigricans (AN) is a rare condition which may affect oral cavity. There are two forms of AN: benign and malignant. Benign AN may be hereditary, or may be related to systemic diseases or drugs. Malignant AN is most often associated with gastric adenocarcinoma but cancers of other sites and types may also occur. This case report is based on a case of a 78-year-old woman suffering from invasive bladder papillary transitional cell carcinoma accompanied by extensive papillomatous areas of normal mucosal color and soft consistency involving the lips, buccal mucosa and hard palate. Verrucous changes with tiny pigmented macules were also found on the skin of the right ear auricle. Oral lesions occurred after the tumor had been diagnosed, i.e. after third operation for tumor recurrence. The fifth operation for tumor recurrence resulted in slight improvement of oral changes. It is concluded that the severity of oral changes is in correlation with tumor progression. The occurrence of oral lesions may be an indicator of tumor progression.	bladder
Demethylating agent 5-aza-2'-deoxycytidine enhances susceptibility of bladder transitional cell carcinoma to Cisplatin.	OBJECTIVES: We investigated the effect of 5-aza-2'-deoxycytidine (DAC), a DNA methyltransferase inhibitor, on transitional cell carcinoma (TCC) cell lines, and examined the synergistic suppression of TCC growth by DAC and five chemotherapeutic agents. METHODS: We measured the cytotoxicity of DAC and chemotherapeutic agents against five TCC cell lines using the WST-1 assay, and analyzed the synergy of DAC and these agents by isobolographic analysis. The effects of each single agent or the combined treatment on apoptosis induction and cell cycle arrest were analyzed by flow cytometric analysis. We also investigated caspase activity and PCNA expression to clarify the mechanism of the synergistic actions of DAC and chemotherapeutic agents against TCC. RESULTS: We demonstrated that DAC could significantly increase the susceptibility of TCC cells to cisplatin (CDDP). Synergistic growth suppression by DAC and CDDP was confirmed in all TCC cell lines tested, but not by DAC combined with other chemotherapeutic agents. DAC inhibited proliferation via inducing G2/M cell cycle arrest, whereas CDDP inhibited proliferation via inducing both apoptosis and G2/M arrest. DAC enhanced the CDDP-induced upregulation of caspase activity and antiproliferative effect, resulting in an increase of cells in subG1 and G2/M phases. In addition, the synergy of DAC and CDDP was independent of p53 status in TCC. CONCLUSIONS: The synergy of DAC and CDDP against TCC suggested that combination chemotherapy with these two agents might be a new strategy to improve the clinical response rate of this malignancy, regardless of p53 mutation.	bladder
[Changes and significance of peripheral blood platelet count in tumor shrinkage induced by a low dose of CTX in T739 mice].	AIM: To establish a mouse model for BTT739 tumor-bearing mice cured by a low dose of cyclophosphamide (CTX). And then to observe the dynamic changes and significance of peripheral blood counts especially blood platelet count during tumor shrinkage induced by a low dose of CTX in T739 mice. METHODS: Mouse bladder carcinoma tissues were inoculated subcutaneously into T739 mice. Seven days later, different doses of CTX or the same volume of NS were administered intraperitoneally to treat these tumor-bearing T739 mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of CTX that could cure most of these tumor-bearing mice. Then another 12 tumor-bearing mice were randomly divided into 15 mg/kg CTX treatment group and control group. Blood samples were obtained from orbital venous sinus on different times after CTX treatment. Complete blood counts were performed and the relationship between peripheral blood platelet counts and tumor shrinkage was analyzed. RESULTS: Within 2 weeks after CTX treatment, the speed of tumor shrinkage had a positive relationship with the dose of CTX used; but the survival rate of the tumor-bearing mice had a negative relationship with the dose of CTX used in 2 months after CTX treatment. 15 mg/kg CTX could cure most of the tumor bearing mice, while it had no remarkably inhibitive effects on peripheral blood cells. The perpherial platelet count increased to (1483.4+/-184.4)x10(9)/L in mice 6 h after CTX treatment. There was significant difference compared with that in mice of control group (1086.6+/-81.0)x10(9)/L (P<0.01). During the 2nd to 14th day after CTX treatment, there was no obvious difference in the platelet count between treatment group and control group (P>0.05). CONCLUSION: CTX 15 mg/kg could cure most of bladder tumor-bearing T739 mice. The transient increase of the peripheral platelet count in 6 h after CTX treatment may relate to the antitumor effects of CTX.	bladder
A prospective study of the determinants of exercise in bladder cancer survivors using the Theory of Planned Behavior.	GOALS OF WORK: Although exercise has gained recognition as an effective supportive care intervention for cancer survivors, exercise participation rates are low. The present study examined the determinants of exercise in bladder cancer survivors using the Theory of Planned Behavior (TPB). PATIENTS AND METHODS: Bladder cancer survivors (N = 397) residing in Alberta, Canada completed a mailed questionnaire at baseline that assessed demographic, medical, behavioral, and social cognitive variables and a second questionnaire 3 months later that assessed exercise. Multiple regression was the primary analysis. MAIN RESULTS: Adjuvant therapy (r = -0.10, p = 0.021), cancer invasiveness (r = -0.10, p = 0.051), and age (r = -0.11, p = 0.037) were all negatively associated with exercise. Intention (beta = 0.25, p < 0.001), perceived behavioral control (beta = 0.18, p = 0.001), and planning (beta = 0.12, p = 0.018) explained 20.9% of the variance in exercise over a 3-month period. Perceived behavioral control (beta = 0.32, p < 0.001), affective attitude (beta = 0.18, p = 0.002), instrumental attitude (beta = 0.15, p = 0.025) and descriptive norm (beta = 0.10, p = 0.032) explained 39.1% of the variability in exercise intention. Constructs from the TPB mediated the associations between adjuvant therapy, cancer invasiveness, age, and exercise. Age and adjuvant therapy also moderated some of the associations within the TPB. CONCLUSIONS: Some medical and demographic variables predict exercise behavior in bladder cancer survivors, but these associations are mediated by the TPB. Interventions based on the TPB may be effective for promoting exercise in this cancer survivor population.	bladder
Sunitinib malate is active against human urothelial carcinoma and enhances the activity of cisplatin in a preclinical model.	PURPOSE: Sunitinib malate (Pfizer, Inc.) is a multitargeted kinase inhibitor that inhibits vascular endothelial growth factor (VEGF) receptor (R)-1, 2 and 3, platelet-derived growth factor receptors (PDGFR)-alpha and beta, Flt3, RET, and Kit. Angiogenesis and VEGF expression correlate with poor outcomes in human urothelial carcinoma. We designed a preclinical study to examine the efficacy of sunitinib alone and in combination with cisplatin against human urothelial carcinoma. DESIGN: The in vitro activities of sunitinib and cisplatin alone and in combination were determined against human urothelial carcinoma cell lines, TCC-SUP and 5637. Antitumor activities were also determined in vivo against murine subcutaneous 5637 xenografts. Immunohistochemistry (IHC) was performed to detect VEGFR2 and Kit, and modulation of proliferation, apoptosis, and angiogenesis. RESULTS: Both cell lines expressed VEGFR2, but did not express Kit. Sunitinib displayed activity against both cell lines in vitro at low micromolar concentrations, which are not attainable in vivo, and was synergistic with cisplatin. Activity was observed for sunitinib at 20 and 40 mg/kg orally once daily for 4 weeks, which attains low nanomolar concentrations in vivo against murine 5637 xenografts. Sunitinib 20 mg/kg/d in combination with cisplatin 4 mg/kg/wk intraperitoneally induced tumor regression compared to no therapy (P < 0.0001) or cisplatin alone (P = 0.06). Cisplatin, sunitinib, and combination treated tumors displayed significantly reduced ki-67 expression compared with control untreated tumors, and the difference was also statistically significant for the combination compared with cisplatin. Cleaved caspase-3 expression was significantly higher for sunitinib single agent and combination therapy compared with untreated controls, and for combination therapy compared with cisplatin alone. CD31 expression was diminished for both single agents and combination therapy compared with untreated tumors. CONCLUSIONS: Sunitinib is preclinically active against urothelial carcinoma, and enhances the activity of cisplatin probably by targeting the stroma.	bladder
[Treatment for urologic polyneoplasia].	An original method of surgical treatment of synchronous primary-multiple bladder and prostate cancer was used in 10 cases. Ureterocutaneostomy with pelvic-iliac lymphodissection appeared to be the simplest means of urine diversion after cysto-prostate-vesiculoectomy, particularly, in apparent concomitant pathology, basal renal insufficiency or blockade. Urine diversion is best assured via ureterosigmorectoanastomosis which is optimal as far as social rehabilitation of the patient is concerned.	bladder